This invention relates generally to the field of automation, and in particular to the use of automated equipment to transfer items. More specifically, the invention relates to the automated transfer of array cartridges into and out of an imaging apparatus.
1. Polymer Arrays
Methods for using arrays of polymers to identify receptors with specific affinities for one of the polymers in the array are known. For example, one method uses immobilized antibodies to analyze binding to peptide ligands or vice-versa. Another type of method uses immobilized oligonucleotides to analyze hybridization to a target nucleic acid. For instance, U.S. patent application Ser. No. 08/624,312, filed Mar. 26, 1996, the complete disclosure of which is herein incorporated by reference, describes apparatus and methods for carrying out repeated hybridizations of a target nucleic acid to an array of nucleic acid probes. Such polymer arrays are described in, e.g., U.S. Pat. No. 5,143,854 and published PCT Application Nos. WO90/15070 and WO92/10092, the complete disclosures of which are herein incorporated by reference. These polymer arrays are nucleic acid arrays which include a plurality of different polynucleotides coupled to a substrate in different known locations.
In one exemplary arrangement, such arrays are packaged within a housing or cartridge, like those described in, e.g., U.S. Pat. No. 5,945,334, and in copending U.S. patent application Ser. Nos. 08/624,312, previously incorporated by reference, 08/528,173, filed Sep. 19, 1995, and published PCT Application No. WO95/33846. As described at col. 4, lines 1-11 of U.S. Pat. No. 5,945,334, a probe is a surface-immobilized molecule that is recognized by a particular target and is sometimes referred to as a ligand. Examples of probes that can be investigated by this invention include, but are not restricted to, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, hormones (e.g., opioid peptides, steroids, etc.), hormone receptors, peptides, enzymes, enzyme substrates, cofactors, drugs, lectins, sugars, oligonucleotides or nucleic acids, oligosaccharides, proteins, and monoclonal antibodies. The disclosures of all of these references are herein incorporated by reference. In brief, such a cartridge may be constructed of a body having a reaction cavity or hybridization chamber. The array or substrate is mounted over the cavity on the body such that the front side of the array substrate, e.g., the side upon which the polynucleotides are situated, is in fluid communication with the cavity. The cartridge includes inlet and outlet ports to allow various fluids to be introduced into and removed from the hybridization chamber.
2. Imaging
Imaging the polymer arrays may be accomplished, for example, by placing the cartridges into a scanning device, such as the GeneArray scanner, available from Affymetrix, Inc. Techniques for imaging polymer arrays are described in U.S. Pat. Nos. 5,834,758 and 5,578,832, the complete disclosures of which are herein incorporated by reference.
In many cases, it is desirable to maintain the cartridges in a temperature controlled environment. Hence, a need exists for equipment and techniques to transfer cartridges from a temperature controlled environment for placement into the scanner in an organized and efficient manner, and for the return of the cartridges to the temperature controlled environment following imaging. Hence, the invention is related to apparatus and methods to facilitate imaging of array cartridges in such a manner.
In one embodiment, a device for transporting cartridges comprises a housing for holding a plurality of cartridges in a temperature controlled environment. The device further includes a transport system having a grasping mechanism to grasp one of the cartridges, to remove the cartridge from the housing and to place the cartridge into a scanner. In this way, each cartridge remains within a temperature controlled environment until ready for scanning. At such time, the transport system is employed to remove the cartridge from the housing and to place the removed cartridge into the scanner.
In one aspect, the device further includes a heating station for heating a cartridge (to prevent fogging) prior to insertion into the scanner. As such, the grasping mechanism may be configured to place the grasped cartridge at the heating station prior to placement into the scanner. In one specific aspect, the heating station may include a fan that is disposed to blow ambient air onto the cartridge to heat the cartridge.
In another aspect, the device may also include a holding station to hold a cartridge after being removed from the scanner. In this way, a cartridge that is removed from the scanner may be positioned near the scanner during a cycle where another cartridge is removed from the heating station and placed into the scanner. The cartridge that is held in the holding station may then be placed back into the housing. In this manner, the throughput of the device may be increased by reducing the amount of travel by the grasping system while the scanner is idle, i.e. awaiting a new cartridge.
Conveniently, a rack system may be rotatably disposed within the housing and may include a plurality of racks for holding the cartridges. In one aspect, a plurality of carriers may be provided, with each carrier holding multiple cartridges. In this way, a carrier of cartridges may conveniently be placed into the housing and coupled to the rack system simply by inserting the carrier into one of the racks. Conveniently, a belt may be coupled to the rack system, and a motor may be used to rotate the belt, thereby rotating the rack system. By rotating the rack system, one or more carriers may be aligned with an opening in the housing to facilitate removal of the cartridges. In a particular aspect, the carriers may each have a bottom end and an open top end, and a plurality of slots for receiving the cartridges in a parallel arrangement. When inserted into the slots, the cartridges extend above the top ends of the carriers to facilitate easy gasping and removal from the carriers. Further, the rack system may be configured to maintain the top ends of the carriers generally horizontal during rotation. In this way, the cartridges will not fall out of the carriers when rotated within the housing. Such a feature may be accomplished by use of belts that maintain alignment of the individual racks during rotation by the motor.
In another aspect, the device may include a barcode reader that is disposed within the housing. In this way, barcode labels on the cartridges may be read as they are removed from and/or placed into the housing. In one aspect, the grasping mechanism comprises a pair of fingers that are movable toward and away from each other to grasp and release the cartridges. In still another aspect, the transport system may comprise a horizontal lead screw and a first motor to rotate the horizontal lead screw. With such a configuration, the grasping mechanism may be coupled to the horizontal lead screw such that rotation of the lead screw translates the grasping mechanism horizontally. Further, a vertical lead screw may be provided along with a second motor to rotate the vertical lead screw. The grasping mechanism may be coupled to the vertical lead screw such that rotation of the lead screw translates the grasping mechanism vertically. A controller may then be employed to operate the motors and the grasping mechanism when transporting the cartridges. Conveniently, the housing may include a lid, and an electric motor may be used to open the lid, such as when receiving a signal from the controller. In this way, the housing may remain closed until a cartridge is removed from or placed into the housing. Alternatively, the lid may be slid open and closed by some interaction of the horizontal travelling system and the lid, i.e. the interaction could push the lid to the side.
The invention further provides an alignment mechanism for aligning a scanner with transporting device, such as the transporting device just described. The alignment mechanism comprises a clamping plate that may be clamped to a portion of the scanner. For example, the alignment mechanism may be clamped to a pair of feet on the bottom of the scanner. An adjustment plate is slidably coupled to the clamping plate and has at least one connector that may be connected to the transporting device, thereby coupling the scanner to the transporting device. An alignment fixture is removably coupled to the adjustment plate and includes an arm that is adapted to be aligned with an entry port of the scanner. In this way, the scanner may be moved relative to the transport device until the alignment fixture is aligned with the entry port. A securing mechanism may then be operated to secure the adjustment plate to the clamping plate, thereby fixing the position of the scanner relative to the transporting device. The alignment fixture may then be removed from the adjustment plate. Alternatively, the transporting device and the scanner may be aligned without the use of an alignment mechanism. Hence, the invention is not intended to be limited for use only with an alignment mechanism.
The invention further provides a method for transporting cartridges. According to the method, a plurality of cartridges are placed into a temperature controlled housing. One of the cartridges is grasped and removed from the housing with a grasping mechanism, moved to the scanner and then placed into the scanner. The grasping mechanism is then opened to deposit the cartridge into the scanner.
In one step, the cartridges are rotated within the housing to align groups of the cartridges with an opening in the housing to facilitate removal of the cartridges. In another step, each cartridge is placed in a warming station prior to being deposited into the scanner. For example, ambient air may be blown onto the cartridge to warm the cartridge and preventing fogging of the cartridge when within the scanner. After scanning, the cartridge is removed from the scanner and placed back into the housing, and another cartridge is placed into the scanner.
In an alternative aspect, to increase throughput the cartridge may be placed in a holding station after removal of the cartridge from the scanner. For example, one cartridge may be placed into the scanner prior to replacing a removed cartridge that is held within the holding station back into the housing. In this way, the grasping mechanism may return to the warming station to find a new cartridge for the scanner after removing a cartridge from the scanner. The grasping mechanism may then deposit the new cartridge into the scanner and return the cartridge that is held at the holding station back to the housing. While at the housing, another cartridge may then be removed and placed into the warming station to complete the cycle. In this way, the amount of travel of the grasping mechanism is minimized while the scanner is sitting idle, i.e. awaiting another cartridge, to increase throughput.
In another step, a barcode label on the cartridge may be read upon removal of the cartridge from the housing to keep track of which cartridges have been removed and scanned. In yet another step, the housing is aligned with the scanner and the housing is secured to the scanner prior to use.
In an alternative embodiment, a method for transporting cartridges comprises placing a plurality of cartridges into a carrier such that the cartridges extend above the carrier. One of the cartridges is removed from the carrier with a grasping mechanism and is moved to the scanner. The cartridge is placed into the scanner, and the grasping mechanism is released to deposit the cartridge into the scanner.